Béquet Yentl, van der Hoorn Marie-Louise, Eikmans Michael, Van der Molen Renate, le Cessie Saskia, van Geloven Nan, van den Akker-van Marle Elske, Vermeulen Marloes, van den Berg Merel, de Bruin Jan-Peter, Cantineau Astrid, Huppelschoten Dana, Meuleman Tess, Mulders Annemarie, Al-Nasiry Salwan, Teklenburg Gijs, Verhoeve Harold, Visser Jantien, van der Zanden Moniek, Goddijn Mariëtte, Lashley Eileen
Department of Gynecology and Obstetrics, Leiden University Medical Center, Leiden, Zuid-Holland, The Netherlands
Department of Gynecology and Obstetrics, Leiden University Medical Center, Leiden, Zuid-Holland, The Netherlands.
BMJ Open. 2025 Jun 19;15(6):e096545. doi: 10.1136/bmjopen-2024-096545.
Recurrent pregnancy loss (RPL) is defined as the occurrence of two or more spontaneous pregnancy losses from the time of conception until 24 weeks of gestation. Currently, an underlying cause can be identified in only a minority of the losses. Potentially, an impaired maternal immune response targeting the semiallograft pregnancy may lead to miscarriage. While prior studies have explored the use of immune-suppressing corticosteroids to modulate the maternal immune system and hopefully improve pregnancy outcome, the absence of sufficiently powered randomised controlled trials (RCT) underscores the need for further research. The primary aim of this study is to evaluate if prednisolone administration in early pregnancy (20 mg daily for 6 weeks, then tapering doses for 2 weeks) in women with unexplained RPL leads to a higher live birth rate (LBR) in comparison to placebo. Additionally, the study assesses the tolerability, safety and the cost-effectiveness of this intervention. Finally, we will explore the effect of prednisolone in various subgroups (based on maternal age, number of previous pregnancy losses, presence of specific antibodies and pre-pregnancy endometrial immune cell level).
This ongoing multicentre, double-blind RCT will randomise 490 women with unexplained RPL and pregnancy <7 weeks to receive either prednisolone or placebo. Each participant will be followed up for 1 year, with digital questionnaires to assess depression, anxiety, medical expenses and productivity loss. We will also collect data on maternal and paternal demographics and neonatal outcomes. The sample size of 490 participants was calculated according to a minimally important increase in LBR of 12% (expecting a LBR of 63% in the general RPL population), including loss to follow-up (estimated at 5%). The analysis will follow the intention-to-treat principle.
This study was submitted under the Clinical Trial Regulation (CTR) in Clinical Trials Information System (CTIS) for assessment by the Central Committee on Research Involving Human Subjects (CCMO) under Clinical Trial number: 2023-503220-76-01. It received full approval on 29/01/2024. Study findings will be presented at conferences and published in a peer-reviewed journal. Participants will be informed about the results by publishing them on the publicly available website of the study.
This trial is registered in ClinicalTrials.gov (ID NCT05725512) and in CTIS (2023-503220-76-01).
复发性流产（RPL）定义为从受孕到妊娠24周期间发生两次或更多次自然流产。目前，只有少数流产能找到潜在病因。针对半同种异体妊娠的母体免疫反应受损可能会导致流产。虽然先前的研究探讨了使用免疫抑制性皮质类固醇来调节母体免疫系统并有望改善妊娠结局，但缺乏足够有力的随机对照试验（RCT）突出了进一步研究的必要性。本研究的主要目的是评估不明原因复发性流产的女性在孕早期服用泼尼松龙（每天20毫克，持续6周，然后逐渐减量2周）与服用安慰剂相比是否能提高活产率（LBR）。此外，该研究还评估了这种干预措施的耐受性、安全性和成本效益。最后，我们将探讨泼尼松龙在不同亚组（基于产妇年龄、既往流产次数、特定抗体的存在情况以及孕前子宫内膜免疫细胞水平）中的效果。
这项正在进行的多中心、双盲随机对照试验将把490名不明原因复发性流产且妊娠<7周的女性随机分为两组，分别接受泼尼松龙或安慰剂治疗。每位参与者将接受为期1年的随访，通过数字问卷评估抑郁、焦虑、医疗费用和生产力损失情况。我们还将收集有关母体和父体人口统计学以及新生儿结局的数据。根据活产率至少提高12%（预计一般复发性流产人群的活产率为63%）来计算490名参与者的样本量，其中包括失访情况（估计为5%）。分析将遵循意向性分析原则。
本研究已根据临床试验法规（CTR）提交至临床试验信息系统（CTIS），由涉及人类受试者研究中央委员会（CCMO）进行评估，临床试验编号为：2023 - 503220 - 76 - 01。于2024年1月29日获得完全批准。研究结果将在会议上展示并发表在同行评审期刊上。研究结果将在研究的公开网站上发布，以便让参与者知晓。
本试验已在ClinicalTrials.gov（ID NCT05725512）和CTIS（2023 - 503220 - 76 - 01）注册。
